Language representation and presurgical language mapping in pediatric epilepsy: A narrative review

As one of the most common neurological diseases in children, epilepsy affects 0.9–2% of children. Complex interactions among the etiologies of epilepsy, interictal discharges, seizures, and antiepileptic drugs lead to cognitive impairments in children with epilepsy. Since epilepsy is considered as a network disorder, in which seizures have a widespread impact on many parts of the brain, childhood epilepsy can even affect the normal development of language. About 25% of children with epilepsy do not respond to medications; therefore, brain surgery is considered as a treatment option for some of them. Presurgical neuropsychological evaluations including language mapping are recommended to preserve cognitive and language abilities of patients after surgery. Functional magnetic resonance imaging as a non-invasive technique for presurgical language mapping has been widely recommended in many epileptic centers. The present study reviewed language representation and presurgical language mapping in children with epilepsy. Mapping language in children with epilepsy helps to localize the epileptogenic zone, and also, to predict the cognitive outcome of epilepsy surgery and possible cognitive rehabilitation. This review collected information about language representation and language mapping in pediatric epilepsy settings.


Introduction
As a neurological disease, recurrent and unprovoked seizures are the main symptoms of epilepsy (1). Epilepsy has been classified into two broad categories: generalized and focal seizures (2). Generalized Iran J Child Neurol. Summer 2020 Vol. 14 No. 3 Received: 02-Jan-2020 Last Revised: 09-Jan-2020 Accepted: 14-Jan-2020 epileptic seizures are conceptualized as originating at some point within, and rapidly engaging, bilaterally distributed networks (3,4 ). On the other hand, a focal seizure starts in a distinct region (epileptogenic zone) and spreads locally to affect one part of the brain. It may become secondarily generalized to the whole brain (3 ). As one of the most common neurological diseases in children, epilepsy affects 0.9-2% of children (3). Pediatric and so on) and adolescence to adult onset (juvenile absence epilepsy and mesial temporal lobe epilepsy with hippocampal sclerosis) [for more details, see (5)].

Cognition and language in pediatric epilepsy
Complex interactions among the etiologies of epilepsy, interictal discharges, seizures, and antiepileptic drugs lead to cognitive impairments in epilepsy (6 Moreover, changes in genome, gene expression, receptor characteristics, and peptides along with brain injury are responsible for both seizures and functional abnormalities underlying cognitive impairment (7 ).
Frequent focal interictal discharges affecting the perisylvian regions, without any significant brain lesion or neurologic history, are the main characteristics of benign epilepsy of childhood with centrotemporal spikes (BECTS), which is a localization-related seizure disorder (8). About 15-25% of cases of pediatric epilepsy suffer from BECTS or Rolandic epilepsy as the most common focal epilepsy syndrome in childhood (9). Seizures stopping after puberty are considered as benign.
Affected children typically have a normal fullscale IQ (10). However, some deficits are reported in neuropsychological features such as language, attention, and memory (11). The majority of educational problems in children with BECTS are attributed to language impairment in the affected children (12).
Children's language development studies started in the 1960s (13). It has been claimed that the same frontal-temporal network is activated in children (14). Moreover, the risk of language impairment has been reported in children with focal epilepsy (15 ).
Since epilepsy is considered as a network disorder, and seizures have a widespread impact on many parts of the brain, childhood epilepsy can affect the normal development of language. It is not known how childhood-onset epilepsy affects functional language networks (16). Language dysfunction is caused by acute seizures or epileptiform discharges, and also occurs in chronic changes to underlying networks (17). Epileptic activity in BECTS may Iran J Child Neurol. Summer 2020 Vol. 14 No. 3 disturb the cerebral organization for language (18).
Whether this language dysfunction is transient in nature or results in a permanent disturbance of language development is a question (19).
It is claimed that a genetic mutation or a structural lesion causes both seizures and language disorders, because even after seizure control, language problems are reported in children with new onset seizures, and are not always resolved (17). Speech and language impairments are rarely observed in children with left hemisphere focal brain injury, which is due to the plasticity of the developing brain. The related factors have been reported as to lesion location, size, and etiology, as well as age at seizure onset (20).
Overvliet et al. (21) stated that language dysfunction could lead to academic underachievement in addition to long-term psychological, social, and professional problems. It has also been claimed that children with poor academic achievement frequently have undiagnosed language difficulties (22). Some recent studies have proposed that there are dorsal and ventral processing streams connecting Broca's area with the temporal and parietal language cortex (23). The ventral stream is implicated in semantic processing, while the dorsal stream is involved in phonological processing, syntactic processing, and working memory (16).
The dorsal auditory processing stream connects regions important for the processing of speech phonemes with regions necessary for expressive production of phonemes in posterior Broca's area (23,24). The dorsal stream translates speech signals into articulatory representations (25). The ventral auditory processing stream links auditory input with conceptual meaning, which is represented across widely-distributed regions (the lexicalsemantic system) (23). Some researchers have reported that developmental aspects of language laterality in typically developing children are not fully characterized (30). Some other researchers have also reported hemispheric differences in infants from the fetal period onward ( 31,32). Language lateralization is also reported in neonates and infants (31 ).
There are contradictory findings about age-related language lateralization. Some studies have reported Iran J Child Neurol. Summer 2020 Vol. 14 No. 3 that lateralization continues to increase with age (33). On the other hand, some other studies have reported that lateralization is comparable to adults at the age six or seven (34). Vargha-Khadem et al. (35) reported that the potential for language relocalization would decrease after the age of five. (36)  regions were less strongly lateralized at the age of ten. They also found that modulatory prefrontalcerebellar regions were the least strongly lateralized, and that the degree of lateralization was not associated with age. Iran J Child Neurol. Summer 2020 Vol. 14 No. 3 Table 1, Speech and Language Disorders (45) Auditory agnosia Inability to recognize the symbolic meaning behind a sound, including an inability to understand speech or meaningful noises (such as a telephone ring) Aphasia Disorders affecting the production or comprehension of spoken and written language due to acquired damage to the language regions of the dominant (typically left) hemisphere. Different components of language are affected depending on the area of brain damage. Although the disorders described below are the canonical aphasias, patients typically have mixed symptoms.

Weiss-Croft and Baldeweg
Receptive/Fluent/Wernicke's Aphasia: Inability to understand spoken or written language, classically attributed to damage of the superior temporal gyrus of the dominant temporal lobe. Speech is fluent but nonsensical.
Expressive/Non-fluent/Broca's Aphasia: Inability to produce speech or writing, classically attributed to damage of the inferior frontal gyrus of the dominant frontal lobe. Speech is halting and grammar is significantly affected, but comprehension is typically spared.
Conduction Aphasia: Inability to repeat secondary to damage to the arcuatefasciculus which connects Wernicke's and Broca's areas.
Dysarthria Impairment of speech due to difficulty with strength or coordination of the muscles of speech. This can be a primary muscle problem or secondary to damage to nerves or brain structures that control the muscles. Mistakes in speech are usually consistent, and there can be difficulty in other functions like chewing or swallowing. Dysarthria can be a congenital or acquired condition.

Prosody
The varying rhythm, intensity, or frequency of speech that, when interpreted as stress or intonation, aids in transmission of meaning.
Dysprosody: Impairment in normal speech intonation patterns.

Speech Dyspraxia/ Apraxia
Difficulty in articulation of syllables or words due to impaired motor planning; mistakes are inconsistent, with intermixed fragments of intact speech. There is often impaired pitch and prosody. Unlike in dysarthria, muscle strength and coordination are otherwise intact. Dyspraxia can be a congenital or acquired condition.

Presurgical evaluation in children with intractable epilepsy
It has been reported that about 25% of children with epilepsy do not respond to medications (47).
Brain surgery is considered as a treatment option for 10 to 50% of patients with intractable epilepsy (Engel, 2018). The main purpose of neurosurgery in pediatric epileptic patients is reduction of the frequency of seizures (20). The major result of this rehabilitation procedure can promote quality of life in these patients. It has been claimed that brain anatomy alone cannot show language areas and may cause risk of injury in epilepsy surgery (45,51). To determine the language locality of the eloquent cortex and laterality, fMRI is recommended as a non-invasive method. The sensitivity and specificity of fMRI for language lateralization are reported to be about 80 and 90%, respectively (17).
fMRI is based on the observation that increased neuronal activity is associated with tightlyregulated and regionally-specific increases in the cerebral blood flow (52). Detecting the location of blood oxygen level dependent MR signal changes induced during cognitive tasks (involving language, memory, and motor control) allows the mapping of neural networks involved in the performance of the tasks (29). Medina et al. (53) reported that fMRI helped identify brain areas related to ictal or interictal activities in children with epilepsy (53). Considering the challenges of fMRI language mapping in clinical settings, the procedure has been recommended to be applied in children with epilepsy, even as young as 5-7 years of age (54).
The most commonly used tasks for presurgical language mapping with fMRI are based on verbal fluency to identify expressive language functions in the dominant hemisphere (29). Verbal fluency paradigms can reliably lateralize language processing in children (55). Verbal fluency requires generating words from given letters (e.g., C, L, F for children; F, A, S for adults), generating words related to specific categories (e.g., food, animals, etc.), or changing a verb to a presented noun (target, ''ball''; response, ''catch, throw, pitch'') (29). It is reported that modified forms of verbal fluency tasks can be used in children as young as five years old (56). Vakharia (57) reported that verbal fluency and verb generation could determine laterality rather than localize language functions precisely.
Language mapping with the same or developmentally -adapted paradigms leads to similar results in children as in adults (29).
Although the general principle of mapping language for children is the same as that for adults, there are many challenges in the mapping process and task design (43).
.To the best of our knowledge, there is no

In Conclusion
Precise presurgical language mapping as a noninvasive method has been proven to be helpful for children with intractable epilepsy to preserve their language abilities after surgery. Moreover, it has been indicated that epilepsy may affect normal language development and laterality in some children. Since possible language impairments can affect social interaction and academic achievements in epileptic children, it is highly essential to know how language is processed and

Authors contribution
Mahdieh Karami: prepared the first draft of the